Interaction between p68 RNA helicase and Ca2+-calmodulin promotes cell migration and metastasis

Abstract

p68 RNA helicase is a prototypical RNA helicase. Here we present evidence to show that, by interacting with Ca-calmodulin, p68 has a role in cancer metastasis and cell migration. A peptide fragment that spans the IQ motif of p68 strongly inhibits cancer metastasis in two different animal models. The peptide interrupts p68 and Ca-calmodulin interaction and inhibits cell migration. Our results demonstrate that the p68-Ca-calmodulin interaction is essential for the formation of lamellipodia and filopodia in migrating cells. p68 interacts with microtubules in the presence of Ca-calmodulin. Our experiments show that interaction with microtubules stimulates p68 ATPase activity. Further, microtubule gliding assays demonstrate that p68, in the presence of Ca-calmodulin, can function as a microtubule motor. This motor activity may allow p68 to transport Ca-calmodulin to the leading edge of migrating cells. © 2013 Macmillan Publishers Limited. All rights reserved.